DESCRIPTION: This is the second revision of a small grant application which proposes to study the relationship between plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activities in gingival tissue obtained from diabetic or non-diabetic rats. Gingival collagenase activity has previously been shown to be increased in periodontal disease and in diabetes. Although the in vivo activators of latent collagenase are unknown, one pathway may involve the action of plasmin, which is generated from plasminogen by the action of PAs, especially tissue plasminogen activator (t-PA). Plasminogen activator activity is in turn down regulated by PA inhibitors (PAI). The balance between PA and PAI may regulate collagenolytic activity. The specific aims are to determine, in diabetic and non-diabetic rats: 1) PA and PAI activities, 2) gingival IL-1 and TNFa activities, and 3) the severity of inflammation, alveolar bone and attachment loss. The long-term goal of these studies is to elucidate the mechanisms of connective tissue breakdown in diabetes-associated periodontal disease.